Abstract: The present invention details the design and operation of a miniaturized device array in which a range of simultaneous mechanical forces are produced by a single external pressure source. The invention is primarily embodied in a microfabricated device arrays designed to rapidly probe biological cell response to various combinations of mechanical, chemical and extra-cellular matrix parameters in a high-throughput fashion.

Abstract: A microplate is provided herein having a plate body with at least one well formed therein, the well having a first open end, a second end, an aperture being formed in the second end, and a side wall extending between the first end and the second end. The microplate further has a permeable membrane extending at least partially across the aperture formed in the second end. A microplate is provided with a permeable membrane which allows not only for removal of certain solutes from a solution (high or low molecular weight solutes), but also allows for separation of macromolecular mixtures and degradation of the membrane. The microplate is also provided with an integrated top assembly or integrated inserts. Also provided herein are methods of culturing systems in the microplates described.

Abstract: This invention provides a means for modifying surface properties of a cell culture substrate under specific conditions, to thereby regulate regions to which cells are allowed to adhere or are not allowed to adhere, depending on cell type. This invention relates to a method of cell culture comprising steps of: applying a positive potential to a conductive region of a substrate comprising a base material having a conductive region and a non-cell-adhesive membrane coupled thereto with the aid of silane, so as to separate the non-cell-adhesive membrane from the substrate; and culturing cells in a region from which the non-cell-adhesive membrane has been separated.

Abstract: A liver sinusoid model includes a generally planar substrate having first and second generally parallel microchannels formed therein. A microporous membrane is disposed between and separating the first and second generally parallel microchannels. A first layer of cells lines one side of the membrane in the first microchannel. The first layer of cells are all a first common cell type. A second layer of cells extends parallel to the first layer of cells in one of the first microchannel and the second microchannel. The second layer of cells is all of a second common cell type. A liver sinusoid bioreactor utilizing the inventive model is also disclosed.

Abstract: A versatile compartmentalized cell culture device, with a selectively permeable membrane separating the compartments, provides many attributes relative to traditional devices. It can be configured for high-density cell culture, co-culture, and sample dialysis while rolling or standing still. It can also be configured for continuous movement of liquid between compartments. The wide combination of attributes not found in other membrane based cell culture and bioprocessing devices includes more cell capacity, more cell secreted product capacity, higher cell and product density, increased medium capacity, minimized use of exogenous growth factors, compatibility with standard cell culture equipment and protocols, increased scale up efficiency, capacity to function when rolling or standing still, capacity for perfusion without the need for pumps, and more efficient sample dialysis.

Abstract: The present invention is based in part on the discovery of significant improvements to cell culture systems and methods in terms of utility and range of application. The system allows for culture of cells in one or more defined spaces within a culture chamber defined by one or more spaced opposing surfaces to provide significant advantages over previously described culture methods. The system includes a chamber for receiving a fluid culture medium; a first surface and one or more second surfaces defining one or more spaces in the chamber; and one or more cells constrained within the one or more spaces. The second surface includes at least one opening for passage of a substance into the culture space.

Abstract: Disclosed are living, three-dimensional tissue constructs for in vitro scientific and medical research, arrays thereof, and methods of making said tissues and arrays.

Abstract: A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications.

Abstract: Thin parylene C membranes having smooth front sides and ultrathin regions (e.g., 0.01 ?m to 5 ?m thick) interspersed with thicker regions are disclosed. The back sides of the membranes can be rough compared with the smooth front sides. The membranes can be used in vitro to grow monolayers of cells in a laboratory or in vivo as surgically implantable growth layers, such as to replace the Bruch's membrane in the eye. The thin regions of parylene are semipermeable to allow for proteins in serum to pass through, and the thick regions give mechanical support for handling by a surgeon. The smooth front side allows for monolayer cell growth, and the rough back side helps prevents cells from attaching there.

Abstract: A method for cultivating a culture of a cell, tissue, etc. There is provided a method of cultivating a culture including a cell or tissue (cell construct), imparting bending motion to the culture. By virtue of applying bending force to a culture of a cell, tissue, etc. (cell construct) to thereby curve the culture, continuous compression and extension in a direction of thickness from a concave portion toward a convex portion thereof are induced. The physical stimulation and deformation not attained by conventional pressurization, shear and tension, then can be loaded on the culture to thereby realize the culture appropriate for restoration of tissue at a region accompanied by bending.

Abstract: The present invention relates to methods of generating an ex vivo tissue-like system in a bioreactor system capable of supporting continuous production of, and output of cells and tissues and an ex vivo tissue system made therefrom.

Abstract: In an embodiment of the disclosure, a biomedical material is provided. The biomedical material includes a biocompatible material having a surface and a carrier distributed over the surface of the biocompatible material, wherein both of the biocompatible material and the carrier have no charges, one of them has charges or both of them have charges with different electricity. The biomedical material is utilized for dentistry, orthopedics, wound healing or medical beauty and applied in the repair and regeneration of various soft and hard tissues.

Abstract: The present disclosure describes a tissue system with conjunctival cells, including conjunctival stem cells. The conjunctival tissue system is derived from isolated tissue comprising conjunctival cells, and is suitable for restoring ocular surface impairments, particularly those that result from damaged or diseased conjunctiva. The tissue system is generated using a simple single medium culture scheme, and a support material, such as human amniotic membrane. The conjunctival tissue system generate is suitable for transplantation to treat the ocular surface of an eye of a subject that is damaged or diseased.

Abstract: A stable system for producing liquid products such as ethanol, butanol and other chemicals from syngas components contacts CO or a mixture of CO2 and H2 with a highly porous side of an asymmetric membrane under anaerobic conditions and transferring these components into contact with microorganisms contained within bio-pores of the membrane. The membrane side of the membrane utilizes a dense layer to control hydration of the bio-pores with a liquid phase. The gas feed directly contacts the microorganisms in the bio-pores and maximizes their utilization of the syngas. Metabolic products produced by the microorganisms leave the membrane through the side opposite the entering syngas. This system and method establishes a unitary direction across the membrane for the supply of the primary feed source to the microorganisms and the withdrawal of metabolically produced products. The feed and product flow improves productivity and performance of the microorganism and the membrane.

Abstract: A stable method for producing liquid products such as ethanol, propanol, butanol and other chemicals from syngas components that contacts CO or a mixture of CO2 and H2 with a highly porous side of an asymmetric membrane under anaerobic conditions and transfers these components into contact with microorganisms contained within bio-pores of the membrane. A liquid contacting side of the membrane utilizes a dense layer to control hydration of the bio-pores with a liquid phase. The gas feed directly contacts the microorganisms in the bio-pores and maximizes their utilization of the syngas. Metabolic products produced by the microorganisms leave the membrane through the side opposite the entering syngas. This method establishes a unitary direction across the membrane for the supply of the primary feed source to the microorganisms and the withdrawal of metabolically produced products. The feed and product flow improves productivity and performance of the microorganism and the membrane.

Abstract: A manipulation tool is disclosed for producing cell material having multiple biological cells, which have a predefined geometrical arrangement. The tool includes a tool body, whose surface at least partially contacts the cell material, and a setting device for adjusting the tool body by a continuous expansion, so that geometrical properties of the surface change and an interior of the tool body is enlarged. The setting device is adapted to expand the tool body at an advance velocity in a range from 0.1 ?m/h to 1 mm/h.

Abstract: A method of creating a multicellular blood-brain barrier model is disclosed. In one embodiment, the method comprises culturing primary brain microvascular endothelial cells or embryonic stem cell-derived endothelial cells upon a permeable support in the presence of neural progenitor cells.

Abstract: A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications.

Abstract: The present invention relates to devices, systems and methods for measuring cell barrier function. In particular, the present invention relates to microfluidic devices for use in in vitro models of the blood-brain barrier and modeling the transport across this barrier.

Abstract: A method for culturing hepatocytes, wherein hepatocytes embedded in an extracellular matrix is placed on a gas-permeable membrane and the hepatocytes are cultured while being supplied with oxygen from the gas-permeable membrane side. By this, the polarity in the hepatocytes can be induced and a bile canaliculus can be formed in a short period of time. Further, the formed polarity can be maintained for a longer period.

Abstract: A device for culturing, storing and expanding adherent renal cells. The device permits the adhesion and proliferation of the cells and the surface characteristics of the membrane material used in said device further permit the cellular matrix components (EMC). A method for expanding adherent renal cells and methods of using particular membranes for culturing, storing and expanding adherent renal cells. The membranes comprise a copolymer of acrylonitrile and sodium methallyl sulfonate as well as polyethylenimine.

Abstract: The present invention relates to a membrane comprising at least one positively charged, synthetic, hydrophobic polymer, at least one hydrophilic polymer and at least one plasticizer; wherein said membrane is flexible and is capable of supporting at least one of cell adherence, cell proliferation or cell differentiation. The invention further relates to use of a membrane of the invention in the preparation of an implantable devices including cell delivery systems, cell growing surfaces and scaffolds. The invention further provides methods for promoting tissue regeneration in a defected tissue region applying membranes of the invention.

Abstract: In the present invention cells are placed in a multiwell plate and grown. When the assay is to be performed, one uses gravity to wash away any unbound ligands rather than vacuum or centrifugation. The cells are then examined to detect the bound ligand. To perform the washing step(s) the plate is placed into a carrier plate having open wells in register with the wells of the filter plate or one may use a wicking device or an underdrain attached to the bottom of the filter plate. Sufficient wash liquid is added to allow for filtration by the effect of gravity to occur. Cells are retained within the wells at a rate of 4 times that of other rapid methods.

Abstract: Synthetic peptide including the sequence KKLRIKSKEK (SEQ ID 1) or a sequence of identical size, in which the K residue (in position 1) and the R residue (in position 4) are conserved, the sequence being able to bind to the syndecan-1 receptor.

Abstract: Gas permeable devices and methods are disclosed for cell culture, including cell culture devices and methods that contain medium at heights, and certain gas permeable surface area to medium volume ratios. These devices and methods allow improvements in cell culture efficiency and scale up efficiency.

Abstract: A disposable apparatus for cell expansion, having at least one bioreactor. The bioreactor has a cellular growth area and a supply area, the cellular growth area being separated from said supply area by a membrane. A fluid recirculation path in fluid communication with the cellular growth area allows for hermetically removing a sample containing cellular matter. This may comprise an elongated tube, or a plurality of parallel tube segments. The parallel tube segments have inflow ends and outflow ends, and the inflow ends are joined at a first common juncture and the outflow ends are joined at a second common juncture. The common junctures may comprise valves.

Abstract: Gas permeable devices and methods are disclosed for cell culture, including cell culture devices and methods that contain medium at heights, and certain gas permeable surface area to medium volume ratios. These devices and methods allow improvements in cell culture efficiency and scale up efficiency.

Abstract: Gas permeable devices and methods are disclosed for cell culture, including cell culture devices and methods that contain medium at heights, and certain gas permeable surface area to medium volume ratios. These devices and methods allow improvements in cell culture efficiency and scale up efficiency.

Abstract: The present invention relates to methods for the design and fabrication of biological constructs, such as organ simulants or organ replacements, which contain complex microfluidic architecture. Designs of the present invention provide increased space in the lateral dimension, enabling a large number of small channels for small vessels.

Abstract: Hydrophilic membrane particularly suited for blotting applications, preferably Western blotting. A pre-wet hydrophobic membrane substrate, preferably made of PVDF, is contacted with a monomer solution and subjected to a UV-initiated free radical polymerization step to render the substrate permanently hydrophilic. The resulting membrane exhibits low background fluorescence, high protein binding, excellent retention of protein sample spot morphology, and extended dynamic range (high signal-to-noise ratio, enhanced sample detectability). The membrane demonstrates comparable or higher performance in Western blotting applications than conventional nitrocellulose Western blotting membranes, particularly for protein detection at low sample concentrations, and is directly water-wettable, eliminating the need for an alcohol pre-wet step prior to use.

Abstract: Bioreactors may be used for the cultivation of cells, in particular of adherent cells, and, in particular for the cultivation and propagation of cell cultures, and utilized in methods for the cultivation of cells. A particular area of application is the use of the bioreactors in the GMP-compliant, fully automatic cultivation and propagation of cells.

Abstract: Disclosed is a device for co-culturing two or more populations of cells using ultrathin, porous membranes positioned between cell culture chambers. Multiple chamber devices and uses thereof are described, including the formation of in vitro tissue models for studying drug delivery, cell-cell interactions, and the activity of low abundance molecular species.

Abstract: A system for culturing cells and/or tissue includes a tissue/cell culture chamber including a tissue/cell culture membrane, at least one collapsible valve fluidly coupled with the tissue/cell culture chamber, a pump fluidly coupled with the tissue/cell culture chamber, and a flow loop including the pump, chamber, and collapsible valve fluidly coupled together.

Abstract: A linear biodevice is provided with fibers that have a curved portion in its cross section approximately perpendicular to the longitudinal direction and approximately spherical adhesive cells that adhere to the periphery of the fiber. A membrane-like biodevice is provided with a sheet that has an opening and approximately spherical adhesive cells that adhere to the opening. A curved portion is present in the cross section on an inner edge of the opening. A bioreactor is provided with a membrane-like biodevice in which spherical adhesive cells grow densely so as to close the openings of the sheet.

Abstract: The invention relates to a membrane which can be used for cultivating adherent or suspension cells, in particular adherent cells, wherein said membrane allows for the adhesion and proliferation of the cells due to modification of the membrane surface with a combination of at least one extracellular matrix protein, at least one extracellular matrix (proteo-) glycan, and at least one heparin-binding growth factor. The invention further relates to a method for preparing said modified or coated membrane which can be used for the cultivation of cells, in particular adherent cells, and to methods of using such membrane for the cultivation of cells, in particular adherent cells.

Abstract: Provided herein are skin substitutes suitable for use in a living subject for purpose of repairing damaged tissues, methods of producing the skin substitutes and their uses. A biocomposite membrane comprising poly(?-caprolactone) (PCL) and at least one material selected from collagen and gelatin is provided. In one embodiment, the biocomposite is a 2-component membrane of PCL and gelatin. In another embodiment, the biocomposite is a 3-component membrane of PCL, collagen and gelatin. The bio-composite membrane may be used directly in vivo as a wound dressing, or as a support for cell growth on each side of the membrane to produce an in vitro cultivated artificial skin for future in vivo and/or in vitro applications.

Abstract: A method for culturing microtissue is provided. The method includes steps of: (a) forming a pattern microarray on a hydrophobic film; (b) adhering the hydrophobic film to a carrier; (c) disposing a plurality of cells on the hydrophobic film for culturing depending on the pattern microarray, and forming a plurality of hair follicle microtissues.

Abstract: A microplate is provided herein having a plate body with at least one well formed therein, the well having a first open end, a second end, an aperture being formed in the second end, and a side wall extending between the first end and the second end. The microplate further has a permeable membrane extending at least partially across the aperture formed in the second end. A microplate is provided with a permeable membrane which allows not only for removal of certain solutes from a solution (high or low molecular weight solutes), but also allows for separation of macromolecular mixtures and degradation of the membrane. The microplate is also provided with an integrated top assembly or integrated inserts. Also provided herein are methods of culturing systems in the microplates described.

Abstract: The invention relates to the field of cell and tissue culture. In particular, the invention provides methods for culturing cells to form aggregates, including stem cells and primary cells. A method for culturing cells according to the invention comprises the steps of: (i) incubating a cells in a hanging drop on the underside of a porous membrane to form aggregates of cells; (ii) inverting the membrane so that the aggregates of cells are located on the upperside of the membrane; and (iii) incubating the aggregates of cells on the upperside of the membrane.

Abstract: A membrane for cultivating adherent or suspension cells, in particular adherent cells. The membrane permits adhesion and proliferation of the cells due to the irradiation of the wet or dry membrane with gamma or beta rays or an electron beam in a dose of from 12.5 to 175 kGy in the presence of oxygen. The resulting membrane may be used without any pre-treatment with surface-modifying substances. A method for preparing such an irradiated membrane for cultivating adherent or suspension cells. Methods of using such a membrane for cultivating adherent or suspension cells.

Abstract: The invention relates to a membrane for supporting cells, especially RPE cells. The membrane is useful in the treatment of conditions such as age related macular degeneration.

Abstract: It is an object of the present invention to provide a cell culture carrier for producing a cell sheet that can be readily detached from a cell culture carrier and is inhibited from contracting after being detached. The cell culture carrier 1 of the present invention comprises: a support-held culture membrane 4 comprising an organic thin film 2 having cell adhesion properties and biodegradability and a frame-like support 3 fixed on the periphery of the organic thin film for maintaining the dimensions of the organic thin film; and a base substrate 6 having a surface 5 with a static water contact angle of 45° or less, wherein the support-held culture membrane 4 is detachably placed on the surface 5 of the base substrate.

Abstract: Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

Abstract: In the present invention cells are placed in a multiwell plate and grown. When the assay is to be performed, one uses gravity to wash away any unbound ligands rather than vacuum or centrifugation. The cells are then examined to detect the bound ligand. To perform the washing step(s) the plate is placed into a carrier plate having open wells in register with the wells of the filter plate or one may use a wicking device or an underdrain attached to the bottom of the filter plate. Sufficient wash liquid is added to allow for filtration by the effect of gravity to occur. Cells are retained within the wells at a rate of 4 times that of other rapid methods.

Abstract: A well-based flow system for cell culture is described which provides for flow of culture containing compounds for drug screening to be exposed to cells seeded on a membrane. The flow of medium may be planar or radial and means are provided for the removal of waste media through fluid outlets in fluid communication with the assay well plates through conduits. Methods of using the system for cell culture and drug toxicity screening are also provided including coculturing cells such as hepatocytes, stem cells, fibroblasts and smooth muscle cells and selectively exposing cells to test compounds.

Abstract: An immunoisolation patch system, and particularly a patch system comprising multiple immunoisolation microcapsules, each encapsulating biological material such as cells for transplantation, which can be used in the prophylactic and therapeutic treatment of disease in large animals and humans without the need for immunosuppression.

Abstract: A process for producing a tissue transplant construct for reconstructing a human or animal organ. The process may include the steps of: (a) isolation and two-dimensional cultivation of organ-specific tissue cells; (b) application of the organ-specific tissue cells to a biocompatible, collagen-containing membrane; and, (c) cultivation of the organ-specific tissue cells on the membrane with biochemical and mechanical stimulation of the organ-specific tissue cells. Tissue transplant constructs and methods for using tissue transplant constructs are also taught.

Abstract: An article is provided herein for use in seeding cells on at least one filter extending across at least one well of an assay device. The article includes an elastomeric body having spaced-apart first and second surfaces, and at least one channel extending between, and through, the first and second surfaces. The channel is formed to sealingly, and detachably, engage an outer surface of the well with the filter being at least partially encompassed by the channel. Advantageously, with the subject invention, a cell monolayer can be formed on the exterior surface of the filter. The assay device may be a multiwell plate, an insert plate, a column, a test tube, or a pipette.

Abstract: A process for producing a tissue transplant construct for reconstructing a human or animal organ. The process may include the steps of: (a) isolation and two-dimensional cultivation of organ-specific tissue cells; (b) application of the organ-specific tissue cells to a biocompatible, collagen-containing membrane; and, (c) cultivation of the organ-specific tissue cells on the membrane with biochemical and mechanical stimulation of the organ-specific tissue cells. Tissue transplant constructs and methods for using tissue transplant constructs are also taught.

Abstract: Methods and devices for applying hemodynamic patterns to human/animal cells in culture are described. Hemodynamic flow patterns are measured directly from the human circulation and translated to a motor that controls the rotation of a cone. The cone is submerged in fluid (i.e., cell culture media) and brought into close proximity to the cells. Rotation of the cone creates time-varying shear stresses. This model closely mimics the physiological hemodynamic forces imparted on endothelial cells in vivo. A TRANSWELL coculture dish (i.e., a coculture dish comprising an artificial porous membrane) may be incorporated, permitting two, three, or more different cell types to be physically separated within the culture dish environment. In-flow and out-flow tubing may be used to supply media, drugs, etc. separately and independently to both the inner and outer chambers. The physical separation of the cell types permits each cell type to be separately isolated for analysis.